Dichloroacetate treatment resulted in a dramatic drop in the conversion of hyperpolarised 1-13C labelled pyruvate to lactate in human colon carcinoma cells
نویسندگان
چکیده
INTRODUCTION: Dichloroacetate (DCA) is a pyruvate dehydrogenase kinase (PDK) inhibitor and is found to be an anti-cancer agent [1]. It causes the activation of pyruvate dehydrogenase (PDH) and increased glucose oxidation by promoting the influx of acetyl-CoA into the mitochondria and the Krebs cycle [1]. The hyperpolarised C experiment measures the conversion of labelled pyruvate to labelled lactate which has been shown to be proportional to lactate dehydrogenase activity and the availability of cellular NADH, the enzyme co-factor [2]. Conversely, steady state measurements of eupolarised (i.e. unlabelled) lactate production report on the overall flux through glycolysis.
منابع مشابه
Dichloroacetate treatment resulted in altered phospholipid metabolism and compromised tumour bioenergetics in human colon carcinoma xenografts
INTRODUCTION: Dichloroacetate (DCA) is a pyruvate dehydrogenase kinase (PDK) inhibitor and is found to be an anti-cancer agent [1]. PDK is a negative regulator of pyruvate dehydrogenase (PDH). PDH is the key mitochondrial enzyme that determines whether pyruvate formed during glycolysis from glucose will be metabolised to lactate or oxidised in the TCA cycle. Treatment with DCA decreases prolife...
متن کاملHyperpolarized 13C Diffusion MRS of Co-Polarized Pyruvate and Fumarate to Measure Lactate Export and Necrosis
Background: Non-invasive tumor characterization and monitoring are among the key goals of medical imaging. Using hyperpolarized 13C-labelled metabolic probes fast metabolic pathways can be probed in real-time, providing new opportunities for tumor characterization. In this in vitro study, we investigated whether measurement of apparent diffusion coefficient (ADC) measurements and magnetic reson...
متن کاملDifferential modulation of glucose, lactate, and pyruvate oxidation by insulin and dichloroacetate in the rat heart.
Despite the fact that lactate and pyruvate are potential substrates for energy production in vivo, our understanding of the control and regulation of carbohydrate metabolism is based principally on studies where glucose is the only available carbohydrate. Therefore, the purpose of this study was to determine the contributions of lactate, pyruvate, and glucose to energy production in the isolate...
متن کاملNovel Approach Synthesis, Molecular Docking and Cytotoxic Activity Evaluation of N-phenyl-2,2-dichloroacetamide Derivatives as Anticancer Agents
Dichloroacetate (DCA) as a small, cheap and available anticancer agent, is a pyruvate mimetic compound that stimulates the activity of pyruvate dehydrogenase (PDH) enzyme through inhibition of pyruvate dehydrogenase kinases (PDHK1-4). DCA turns on programed cell death (apoptosis) which suppressed in tumor cells and therefore inhibits tumor growth. DCA also interferes with the glucose uses of ca...
متن کاملPossible Involvement of a Specific Cell Surface Receptor for Calprotectin-Induced Apoptosis in Colon Adenocarcinoma and Carcinam Cell Lines (SW742 and HT29/219)
Calprotectin, a calcium-bound protein complex, is abundant in the cytosol of neutrophils. It has been reported that this protein has an apoptotic activity in tumor cells. Since calprotectin increases in colorectal cancer, this study was conducted to investigate, for the first time, the cytotoxicity/apoptotic effect of calprotectin on HT29/219 and SW742 colon carcinoma and adenocarcinoma cell li...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره شماره
صفحات -
تاریخ انتشار 2009